Our results showed that the maximal isometric strength exerted by the forearm muscles in humans is proportional to their size whatever the age, and that VM is the best index of muscle size during growth. The previously reported increased ability to produce maximal strength from childhood to adulthood could be explained by systematic bias introduced by the method used to characterize muscle size instead of physiological or neural changes.

We quantified energy production in 7 prepubescent boys (11.7 ± 0.6 yr) and 10 men (35.6 ± 7.8 yr) using (31)P-magnetic resonance spectroscopy to investigate whether development affects muscle energetics, given that resistance to fatigue has been reported to be larger before puberty. Each subject performed a finger flexions exercise at 0.7 Hz against a weight adjusted to 15% of their maximal voluntary strength for 3 min, followed by a 15-min recovery period. The total energy cost was similar in both groups throughout the exercise bout, whereas the interplay of the different metabolic pathways was different. At the onset of exercise, children exhibited a higher oxidative contribution (50 ± 15% in boys and 25 ± 8% in men, P < 0.05) to ATP production, whereas the phosphocreatine breakdown contribution was reduced (40 ± 10% in boys and 53 ± 12% in men, P < 0.05), likely as a compensatory mechanism. The anaerobic glycolysis activity was unaffected by maturation. The recovery phase also disclosed differences regarding the rates of proton efflux (6.2 ± 2.5 vs. 3.8 ± 1.9 mM · pH unit(-1) · min(-1), in boys and men, respectively, P < 0.05), and phosphocreatine recovery, which was significantly faster in boys than in men (rate constant of phosphocreatine recovery: 1.3 ± 0.5 vs. 0.7 ± 0.4 min(-1); V(max): 37.5 ± 14.5 vs. 21.1 ± 12.2 mM/min, in boys and men, respectively, P < 0.05). Our results obtained in vivo clearly showed that maturation affects muscle energetics. Children relied more on oxidative metabolism and less on creatine kinase reaction to meet energy demand during exercise. This phenomenon can be explained by a greater oxidative capacity, probably linked to a higher relative content in slow-twitch fibers before puberty.

The aim of the present study was to compare the oxidative capacity of the forearm flexor muscles in vivo between children and adults using 31-phosphorus magnetic resonance spectroscopy. Seven boys (11.7 +/- 0.6 y) and 10 men (35.6 +/- 7.8 year) volunteered to perform a 3 min dynamic finger flexions exercise against a standardized weight (15% of the maximal voluntary contraction). Muscle oxidative capacity was quantified on the basis of phosphocreatine (PCr) post-exercise recovery kinetics analysis. End-of-exercise pH was not significantly different between children and adults (6.6 +/- 0.2 vs. 6.5 +/- 0.2), indicating that indices of PCr recovery kinetics can be reliably compared. The rate constant of PCr recovery (kPCr) and the maximum rate of aerobic ATP production were about 2-fold higher in young boys than in men (kPCr: 1.7 +/- 1.2 vs. 0.7 +/- 0.2 min(-1); Vmax: 49.7 +/- 24.6 vs. 29.4 +/- 7.9 mmol.L(-1).min(-1), p < 0.05). Our results clearly illustrate a greater mitochondrial oxidative capacity in the forearm flexor muscles of young children. This larger ATP regeneration capacity through aerobic mechanisms in children could be one of the factors accounting for their greater resistance to fatigue during high-intensity intermittent exercise.

Christie AD, Tonson A, Larsen RG, DeBlois JP, Kent JA. Human skeletal muscle metabolic economy in vivo: effects of contraction intensity, age, and mobility impairment. Am J Physiol Regul Integr Comp Physiol 307: R1124 -R1135, 2014. First published August, 27, 2014; doi:10.1152/ajpregu.00083.2014.-We tested the hypothesis that older muscle has greater metabolic economy (ME) in vivo than young, in a manner dependent, in part, on contraction intensity. Twenty young (Y; 24 Ϯ 1 yr, 10 women), 18 older healthy (O; 73 Ϯ 2, 9 women) and 9 older individuals with mild-to-moderate mobility impairment (OI; 74 Ϯ 1, 7 women) received stimulated twitches (2 Hz, 3 min) and performed nonfatiguing voluntary (20, 50, and 100% maximal; 12 s each) isometric dorsiflexion contractions. Torque-time integrals (TTI; Nm·s) were calculated and expressed relative to maximal fat-free muscle cross-sectional area (cm 2 ), and torque variability during voluntary contractions was calculated as the coefficient of variation. Total ATP cost of contraction (mM) was determined from flux through the creatine kinase reaction, nonoxidative glycolysis and oxidative phosphorylation, and used to calculate ME (Nm·s·cm Ϫ2 ·mM ATP Ϫ1 ). While twitch torque relaxation was slower in O and OI compared with Y (P Յ 0.001), twitch TTI, ATP cost, and economy were similar across groups (P Ն 0.15), indicating comparable intrinsic muscle economy during electrically induced isometric contractions in vivo. During voluntary contractions, normalized TTI and total ATP cost did not differ significantly across groups (P Ն 0.20). However, ME was lower in OI than Y or O at 20% and 50% MVC (P Յ 0.02), and torque variability was greater in OI than Y or O at 20% MVC (P Յ 0.05). These results refute the hypothesis of greater muscle ME in old age, and provide support for lower ME in impaired older adults as a potential mechanism or consequence of age-related reductions in functional mobility. bioenergetics; mitochondria; creatine kinase; glycolysis; oxidative phosphorylation WHILE MANY OF THE CHANGES in neuromuscular properties that occur with advanced age, such as declines in strength and contractile velocity (5, 64), can be detrimental to physical function, some age-related physiological changes may act in a compensatory manner and, thereby, help maintain function to some degree. For instance, it has been suggested that a greater proportion of type I muscle fibers (35,55,56), slowed contractile properties (62, 71), and slower motor unit discharge rates, particularly during maximal contractions (8,12,37,38,68), may place older muscle at an economic advantage (41, 49). While age-related differences in muscle metabolic economy (ME; mass-normalized torque produced per unit ATP consumed) have been shown in rat muscle (13, 32), a systematic analysis of muscle ME in aging humans has only recently begun (41,54). Such a focus on muscle ME is critical to informing studies of age-related changes in the energy cost of whole body activities, such as walking, which generally involve measures of...

Atherosclerosis is an inflammatory disease of arterial walls and the rupturing of atherosclerotic plaques is a major cause of heart attack and stroke. Imaging techniques that can enable the detection of atherosclerotic plaques before clinical manifestation are urgently needed. Magnetic resonance imaging (MRI) is a powerful technique to image the morphology of atherosclerotic plaques. In order to better analyze molecular processes in plaques, contrast agents that can selectively bind to plaque receptors will prove invaluable. CD44 is a cell surface protein overexpressed in plaque tissues, the level of which can be correlated with the risks of plaque rupture. Thus, targeting CD44 is an attractive strategy for detection of atherosclerotic plaques. Herein, we report the synthesis of hyaluronan-conjugated iron oxide nanoworms (HA-NWs). A new purification and gel electrophoresis protocol was developed to ensure the complete removal of free HA from HA-NWs. Compared to the more traditional spherical HA-bearing nanoparticles, HA-NWs had an elongated shape, which interacted much stronger with CD44-expressing cells in CD44- and HA-dependent manners. Furthermore, the HA-NWs did not induce much inflammatory response compared to the spherical HA nanoparticles. When assessed in vivo, HA-NWs enabled successful imaging of atherosclerotic plaques in a clinically relevant model of ApoE knockout transgenic mice for noninvasive plaque detection by MRI. Thus, nanoprobe shape engineering can be a useful strategy to significantly enhance their desired biological properties.

Capsiate is known to increase whole body oxygen consumption possibly via the activation of uncoupling processes, but its effect at the skeletal muscle level remains poorly documented and conflicting. To clarify this issue, gastrocnemius muscle function and energetics were investigated in mice 2 h after a single intake of either vehicle (control) or purified capsiate (at 10 or 100 mg/kg body wt) through a multidisciplinary approach combining in vivo and in vitro measurements. Mechanical performance and energy pathway fluxes were assessed strictly noninvasively during a standardized electrostimulation-induced exercise, using an original device implementing 31-phosphorus magnetic resonance spectroscopy, and mitochondrial respiration was evaluated in isolated saponin-permeabilized fibers. Compared with control, both capsiate doses produced quantitatively similar effects at the energy metabolism level, including an about twofold decrease of the mitochondrial respiration sensitivity for ADP. Interestingly, they did not alter either oxidative phosphorylation or uncoupling protein 3 gene expression at rest. During 6 min of maximal repeated isometric contractions, both doses reduced the amount of ATP produced from glycolysis and oxidative phosphorylation but increased the relative contribution of oxidative phosphorylation to total energy turnover (+28 and +21% in the 10- and 100-mg groups, respectively). ATP cost of twitch force generation was further reduced in the 10- (-35%) and 100-mg (-45%) groups. Besides, the highest capsiate dose also increased the twitch force-generating capacity. These data present capsiate as a helpful candidate to enhance both muscle performance and oxidative phosphorylation during exercise, which could constitute a nutritional approach for improving health and preventing obesity and associated metabolic disorders.

Chronic administration of capsiate is known to accelerate whole-body basal energy metabolism, but the consequences in exercising skeletal muscle remain very poorly documented. In order to clarify this issue, the effect of 2-week daily administration of either vehicle (control) or purified capsiate (at 10- or 100-mg/kg body weight) on skeletal muscle function and energetics were investigated throughout a multidisciplinary approach combining in vivo and in vitro measurements in mice. Mechanical performance and energy metabolism were assessed strictly non-invasively in contracting gastrocnemius muscle using magnetic resonance (MR) imaging and 31-phosphorus MR spectroscopy (31P-MRS). Regardless of the dose, capsiate treatments markedly disturbed basal bioenergetics in vivo including intracellular pH alkalosis and decreased phosphocreatine content. Besides, capsiate administration did affect neither mitochondrial uncoupling protein-3 gene expression nor both basal and maximal oxygen consumption in isolated saponin-permeabilized fibers, but decreased by about twofold the K m of mitochondrial respiration for ADP. During a standardized in vivo fatiguing protocol (6-min of repeated maximal isometric contractions electrically induced at a frequency of 1.7 Hz), both capsiate treatments reduced oxidative cost of contraction by 30-40%, whereas force-generating capacity and fatigability were not changed. Moreover, the rate of phosphocreatine resynthesis during the post-electrostimulation recovery period remained unaffected by capsiate. Both capsiate treatments further promoted muscle mass gain, and the higher dose also reduced body weight gain and abdominal fat content. These findings demonstrate that, in addition to its anti-obesity effect, capsiate supplementation improves oxidative metabolism in exercising muscle, which strengthen this compound as a natural compound for improving health.

The microvasculature is critical in the control of blood flow. Aging and reduced physical activity may both decrease microvascular function. Purpose The primary aim was to evaluate the influence of age on microvascular function in adults with similar physical activity levels (PA). Secondary aims were to assess the reliability of muscle functional MRI in older adults and the relationship between physical activity and microvascular function in older adults. Methods Microvascular BOLD responses were measured in young adults (YA, n=12, 21±1 (±SD) years old, PA=239±73×103 counts/day) and older adults (OA, n=12, 64±4 years old, PA=203±48×103 counts/day). Functional MR images (3T, echo planar blood-oxygen-level dependent (BOLD)), of the leg were acquired following brief (1s) maximal voluntary isometric contractions. Test-retest reliability of BOLD responses and the Pearson correlation between peak BOLD and PA was assessed in a group of older adults (OA-r) with a broad range of PA (66±5 years old, n=9, PA range = 54×103 count/day to 674×103 counts/day). Results Peak BOLD microvascular responses were reduced for OA compared to YA. OA peak BOLD was 27% lower in the soleus (OA: 3.3±0.8% vs. YA: 4.5±1.4% YA, p=0.017) and 40% lower in the anterior compartment (1.6±0.6% OA vs. 2.7±1.1% YA, p=0.006). Coefficient of variation was 8.6% and 11.8% for peak BOLD in the soleus and anterior compartment, respectively, with an intraclass correlation of 0.950 for both muscle regions. The correlation between peak BOLD and PA was r ≥ 0.715, p ≤ 0.030. Conclusions Aging was associated with reduced microvascular function in leg muscles, independent of physical activity. The findings also revealed good reliability for BOLD MRI in older adults for the soleus and anterior compartment muscles.